Cell death

Cell, Journal Year: 2024, Volume and Issue: 187(2), P. 235 - 256

Published: Jan. 1, 2024

Cell death supports morphogenesis during development and homeostasis after birth by removing damaged or obsolete cells. It also curtails the spread of pathogens eliminating infected can be induced genetically programmed suicide mechanisms apoptosis, necroptosis, pyroptosis, it a consequence dysregulated metabolism, as in ferroptosis. Here, we review signaling underlying each cell-death pathway, discuss how impaired excessive activation distinct processes promote disease, highlight existing potential therapies for redressing imbalances cell cancer other diseases.

Language: Английский

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Psoriatic Arthritis: Pathogenesis and Targeted Therapies

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(5), P. 4901 - 4901

Published: March 3, 2023

Psoriatic arthritis (PsA), a heterogeneous chronic inflammatory immune-mediated disease characterized by musculoskeletal inflammation (arthritis, enthesitis, spondylitis, and dactylitis), generally occurs in patients with psoriasis. PsA is also associated uveitis bowel (Crohn’s ulcerative colitis). To capture these manifestations as well the comorbidities, to recognize their underlining common pathogenesis, name of psoriatic was coined. The pathogenesis complex multifaceted, an interplay genetic predisposition, triggering environmental factors, activation innate adaptive immune system, although autoinflammation has been implicated. Research identified several immune-inflammatory pathways defined cytokines (IL-23/IL-17, TNF), leading development efficacious therapeutic targets. However, responses drugs occur different tissues involved, resulting challenge global management disease. Therefore, more translational research necessary order identify new targets improve current outcomes. Hopefully, this may become reality through integration omics technologies that allow better understanding relevant cellular molecular players In narrative review, we aim provide updated overview pathophysiology, including latest findings from multiomics studies, describe targeted therapies.

Language: Английский

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The role of cell death in SARS-CoV-2 infection

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: Sept. 20, 2023

Abstract Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), showing high infectiousness, resulted in an ongoing pandemic termed disease 2019 (COVID-19). COVID-19 cases often experience distress syndrome, which has caused millions of deaths. Apart from triggering inflammatory and immune responses, many viral infections can cause programmed cell death infected cells. Cell mechanisms have a vital role maintaining suitable environment to achieve normal functionality. Nonetheless, these processes are dysregulated, potentially contributing pathogenesis. Over the past decades, multiple pathways becoming better understood. Growing evidence suggests that induction by may significantly contributes infection pathogenicity. However, interaction SARS-CoV-2 with death, together its associated mechanisms, is yet be elucidated. In this review, we summarize existing concerning molecular modulation as well viral-host interactions, shed new light on antiviral therapy against SARS-CoV-2.

Language: Английский

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Proteome-wide Mendelian randomization identifies therapeutic targets for ankylosing spondylitis

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: March 19, 2024

Ankylosing Spondylitis (AS) is a chronic inflammatory disorder which can lead to considerable pain and disability. Mendelian randomization (MR) has been extensively applied for repurposing licensed drugs uncovering new therapeutic targets. Our objective pinpoint innovative protein targets AS assess the potential adverse effects of druggable proteins.

Language: Английский

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Immunogenicity and Loss of Effectiveness of Biologic Therapy for Inflammatory Bowel Disease Patients Due to Anti-Drug Antibody Development

Antibodies, Journal Year: 2024, Volume and Issue: 13(1), P. 16 - 16

Published: Feb. 26, 2024

Many patients with inflammatory bowel disease (IBD) experience a loss of effectiveness to biologic therapy (i.e., anti-TNF therapy, etc.). Therefore, in addition the adverse effects treatment, these also face failure achieve and maintain remission. Immunogenicity, process production antibodies biological agents, is fundamental evolution response treatment IBD patients. The presence linked decreased serum drug levels inhibited activity. However, immunogenicity rates exhibit significant variability across states, immunoassay formats, time periods. In this review, we aimed elucidate immune mechanisms antibody formation biologics, response, clinical results for from systematic reviews meta-analyses, as well summarize most recent strategies overcoming approaches managing IBD.

Language: Английский

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Inflammation in Fabry disease: stages, molecular pathways, and therapeutic implications

Frontiers in Cardiovascular Medicine, Journal Year: 2024, Volume and Issue: 11

Published: June 12, 2024

Fabry disease, a multisystem X-linked disorder caused by mutations in the alpha-galactosidase gene. This leads to accumulation of globotriaosylceramide (Gb3) and globotriaosylsphingosine (Lyso-Gb3), culminating various clinical signs symptoms that significantly impact quality life. Although treatments such as enzyme replacement, oral chaperone, emerging therapies like gene therapy exist; delayed diagnosis often curtails their effectiveness. Our review highlights importance delineating stages inflammation disease enhance timing efficacy interventions, particularly before progression fibrosis, where treatment options are less effective. Inflammation is an important aspect pathogenesis disease. thought be predominantly mediated innate immune response, with growing evidence pointing towards potential involvement adaptive mechanisms remain poorly understood. Highlighted fact shares profiles systemic autoinflammatory diseases, blurring distinctions between these disorders highlighting need for nuanced understanding dynamics. insight crucial developing targeted improving administration current replacement. Moreover, our discusses complex interplay inflammatory processes treatments, challenges posed anti-drug antibodies. These antibodies can attenuate effectiveness therapies, necessitating more refined approaches mitigate impact. By advancing molecular changes, mediators causative factors drive we aim clarify role disease's progression. improved will help us see how fit into landscape Additionally, it guide development effective diagnostic therapeutic approaches, ultimately patient care.

Language: Английский

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The role of antibody glycosylation in autoimmune and alloimmune kidney diseases

Nature Reviews Nephrology, Journal Year: 2024, Volume and Issue: 20(10), P. 672 - 689

Published: July 3, 2024

Language: Английский

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Navigating the Neuroimmunomodulation Frontier: Pioneering Approaches and Promising Horizons—A Comprehensive Review

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(17), P. 9695 - 9695

Published: Sept. 7, 2024

The research in neuroimmunomodulation aims to shed light on the complex relationships that exist between immune and neurological systems how they affect human body. This multidisciplinary field focuses way responses are influenced by brain activity neural function is impacted immunological signaling. provides important insights into a range of medical disorders. Targeting both pathways, neuroimmunomodulatory approaches used clinical pain management address chronic pain. Pharmacological therapies aim modulate neuroimmune interactions reduce inflammation. Furthermore, bioelectronic techniques like vagus nerve stimulation offer non-invasive control these systems, while neuromodulation transcranial magnetic modify neuronal Within context aging, analyzes ways which alterations brought aging contribute cognitive decline neurodegenerative illnesses. Restoring homeostasis through strategies shows promise reducing age-related decline. Research mood disorders dysregulation relates illnesses including anxiety depression. Immune system fluctuations increasingly recognized for their impact function, leading novel treatments target interactions. review emphasizes interdisciplinary cooperation continuous necessary better understand relationship systems.

Language: Английский

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Nitazoxanide reduces inflammation and bone erosion in mice with collagen-induced arthritis via inhibiting the JAK2/STAT3 and NF-κB pathways in fibroblast-like synoviocytes

Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 171, P. 116195 - 116195

Published: Jan. 22, 2024

Our recent study showed that Nitazoxanide (NTZ), an FDA-approved anti-parasitic drug, prevents ovariectomy-induced bone loss by inhibiting osteoclast activity. However, there have been no investigations to determine whether NTZ has preventive potential in other resorbing diseases, especially rheumatoid arthritis (RA). In this study, the primary RA fibroblast-like synoviocytes (RA-FLS) and collagen-induced (CIA) murine model were used evaluate effect of NTZ. The results potently inhibited proliferation, migration invasion capacity RA-FLS a dose dependent manner restraining cell entry into S phases, without induction apoptosis. obviously reduced spontaneous mRNA expression IL-1β, IL-6 RANKL, as well TNF-α-induced transcription IL-6, MMP9 genes. terms molecular mechanism, significantly basal or activation JAK2/STAT3 (T705) NF-κB pathway, but not MAPK STAT3 (S727) phosphorylation. Moreover, ameliorated synovial inflammation erosion CIA mice through reducing production inflammatory mediators formation, respectively. Collectively, our findings indicate exhibits anti-inflammatory anti-erosive effects both ex vivo vivo, which provides promising evidence for therapeutic application novel agent RA.

Language: Английский

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Cytokine Storm-Induced Thyroid Dysfunction in COVID-19: Insights into Pathogenesis and Therapeutic Approaches

Drug Design Development and Therapy, Journal Year: 2024, Volume and Issue: Volume 18, P. 4215 - 4240

Published: Sept. 1, 2024

Angiotensin-converting enzyme 2 receptors (ACE2R) are requisite to enter the host cells for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). ACE2R is constitutive and functions as a type I transmembrane metallo-carboxypeptidase in renin-angiotensin system (RAS). On thyroid follicular cells, allows SARS-CoV-2 invade gland, impose cytopathic effects produce endocrine abnormalities, including stiff back, neck pain, muscle ache, lethargy, enlarged, inflamed gland COVID-19 patients. Further damage perpetuated by sudden bursts of pro-inflammatory cytokines, which suggestive life-threatening known "cytokine storm". IL-1β, IL-6, IFN-γ, TNF-α identified key orchestrators cytokine storm. These inflammatory mediators upregulate transcriptional turnover nuclear factor-kappa B (NF-κB), Janus kinase/signal transducer activator transcription (JAK/STAT), mitogen-activated protein kinase (MAPK), paving pathway storm-induced dysfunctions euthyroid sick syndrome, autoimmune diseases, thyrotoxicosis Targeted therapies with corticosteroids (dexamethasone), JAK inhibitor (baricitinib), nucleotide analogue (remdesivir) N-acetyl-cysteine have demonstrated effectiveness terms attenuating severity frequency dysfunctions, morbidity mortality Here, we review pathogenesis storms mechanisms pathways that establish connection between disorder COVID-19. Moreover, cross-talk interactions signalling therapeutic strategies address COVID-19-associated diseases also discussed herein.

Language: Английский

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